Terpenoid Plant Metabolites - Structural Characterization and Biological Importance

University dissertation from Centre for Analysis and Synthesis, Department of Chemistry, Lund University

Abstract: In response to the challenges of their local environments, organisms produce of a large number of chemical diverse compounds with complex stereochemistry and reactive functional groups. These characteristics enable them to interact and bind specifically to biological target molecules and exert various biological activities, and have assured that Natural products continues to be an important source of bioactive compounds, which, for example, facilitate the search for new lead structures that can be developed into new pharmaceuticals. This thesis describes the isolation by different chromatographic techniques, structure elucidation by NMR spectroscopy and high-resolution mass spectrometry and bioactivity of secondary metabolites of four medicinal plants. Kaunia lasiophthalma G. was found to be particularly rich in sesquiterpene lactones and produced two new eudesmane derivatives (2.1 and 2.2) as well as a novel triterpene with a new carbon skeleton (2.3). The anticancer activity of several of the isolated metabolites was studied towards a panel of five breast-cancer cell lines, and compared with their cytotoxicity in normal-like breast epithelial MCF-10A cells. In addition, demonstrating the importance of the ?-methylene-?-lactone moiety present in most assayed compounds, a methyl cysteine adduct prepared from 2.10 was also evaluated. These compounds tested were found to exhibit different levels of anticancer and cytotoxicity. The isolation and identification of the active constituents from extracts of Trixis antimenorrhoea and Lantana balansae possessing antileishmanial activity was carried out. Two new metabolites, the nortrixane 3.1 and the trixanolide 3.2, and eleven known compounds, terpenoids and flavonoids, were isolated from Trixis antimenorrhoea. Lantana balansae yielded eleven previously discovered metabolites, however, a potent cyclopentenone fatty acid derivative (3.16) and flavanones (3.17 and 3.18) are new classes of secondary metabolites for the genus Lantana. The structures of the compounds and the associated leishmanicidal activity towards L. amazonensis and L. braziliensis are discussed. Three macrocyclic monoterpene O-glycosides (4.1-4.3) isolated from the leaves and small branches of Parkinsonia aculeate L. are reported. The structures were established using NMR and MS techniques. Particularly, 2D NMR experiments, HMQC, HMBC, COSY, TOCSY and ROESY, were crucial for the assembling of the structures.